Data published in The Laryngoscope shows INO 3107 resulted in long-term surgery reduction in recurrent respiratory papillomatosis (RRP)- Inovio Pharmaceuticals

Inovio Pharmaceuticals, a biotechnology company focused on developing and marketing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, announced that peer-reviewed data from a retrospective study investigating the long-term clinical and safety response of patients treated with INO-3107 were published online in The Laryngoscope under the title "DNA Immunotherapy (INO-3107) Results in Long-term Surgery Reduction in Recurrent Respiratory Papillomatosis (RRP).  The data demonstrate that a majority of patients experienced continued improvement, as measured by the number of surgical procedures needed after treatment with INO-3107, beyond the initial 12-month study period of the previously published Phase I/II trial. 

A Phase I/II open-label trial of INO 3107 (RRP 001) in 32 patients, previously published in Nature Communications , demonstrated a statistically significant reduction in the number of surgeries needed to control their RRP when comparing the 12 months following the initiation of treatment with INO 3107 versus the 12 months prior to beginning treatment with INO 3107. The retrospective trial published today in The Laryngoscope (RRP-02) collected data on 28 of the original 32 patients in RRP-001 to assess the longer-term treatment effect of INO 3107. The median follow-up period for both RRP-001 and RRP-002 combined was 2.8 years from treatment initiation. The efficacy assessment was defined by the number of RRP surgical interventions reported. The safety evaluation included reported serious adverse events (SAEs).

Key Results of the Retrospective Trial with INO-3107

• • INO 3107 demonstrated continued clinical effect against RRP that improved over time:
  • • Patients experiencing a 50-100% reduction in surgeries (ORR) increased from 72% at the end of the initial 12-month Phase I/II trial (Year 1) to 86% at the end of the second 12-month period (Year 2)
  • • Patients experiencing a CR (0 surgeries per year) increased from 28% for Year 1 to 50% for Year 2
  • • Mean number of surgeries was reduced from 4.1 in the pre-treatment period (the 52 weeks prior to beginning treatment with INO 3107) to 1.7 for Year 1 to 0.9 for Year 2
  • • Partial data into the third 12-month period (Year 3 - median follow up 2.8 years following initial treatment) continued the trend of improvement and a reduced number of surgeries
• • INO 3107 was well tolerated, with no serious adverse events or long-term safety concerns identified

INO 3107 is designed to elicit an antigen-specific T cell response against both HPV-6 and HPV-11 proteins. These targeted T cells seek out and kill HPV-6 and HPV-11 infected cells, with the aim of potentially preventing or slowing the growth of new papillomas. 

In a Phase I/II trial of 32 participants (RRP-001), 72% of patients saw a 50-to-100% reduction in the number of surgeries after starting treatment with INO 3107 at the end of the first year. A retrospective study involving 28 of the original trial participants (RRP-002) showed this number increasing to 86% at the end of the second 12-month period with no additional dosing. Half of those patients required no surgeries at all. Patients in RRP-001 had a median of 4 surgeries (range: 2-8) in the year prior to dosing. At the outset of the trial (Day 0), patients had a clinically warranted procedure to have papillomas surgically removed, but any surgery performed after Day 0 was counted against the efficacy endpoint. Treatment with INO 3107 generated a strong immune response in the trial, inducing activated CD4 T cells and activated CD8 T cells with lytic potential. T cell responses were also observed at Week 52, indicating a persistent cellular memory response. INO 3107 was well tolerated, with trial participants experiencing mostly low-grade (Grade 1) treatment-emergent adverse effects such as injection site pain and fatigue. Like other DNA medicines, INO 3107 has shown the ability to generate antigen-specific T cells that is not affected by anti-vector immunity impacting immunogenicity, either before administration or after the first dose, unlike other T cell generating platforms such as viral vectors. This feature of DNA medicines is anticipated to allow INO 3107 to maintain T cell response and overall efficacy, which could make it an important therapeutic option for a majority of RRP patients.

Understanding how much every single surgery matters to patients, it is compelling to see the vast majority of patients experienced significant benefit from treatment with INO-3107, resulting in a reduction in the number of surgeries required to control their disease — a benefit that continued and often improved over time," said Dr. Jacqueline Shea, Inovio's President and Chief Executive Officer. "The sustained reduction in surgery following treatment with INO-3107 demonstrated here is central to our belief that INO-3107 could become the preferred product on the market, if approved""

"The most important takeaway from this data is that the majority of patients experienced a reduction in surgeries following initial treatment with INO-3107, and almost all of those patients maintained or improved their response 2 years after initial treatment," said Dr. Aaron Friedman, Associate Professor of Clinical Otolaryngology, Head and Neck Surgery, University of Cincinnati Medical Center, and a principal investigator on the trial. "With this continued improvement in clinical effect, we believe INO-3107 has the potential to change the trajectory of a patient's disease and set a new standard of care for the RRP community."

See  citations- Amin MR, Belafsky PC , Best, SR et al. DNA Immunotherapy (INO-3107) Results in Long-Term Surgery Reduction in RRP. The Laryngoscope 2025: 1–9, https://doi.org/10.1002/lary.32416.

Morrow MP., Gillespie E., Sylvester A. et al. DNA immunotherapy for recurrent respiratory papillomatosis (RRP): phase 1/2 study assessing efficacy, safety and immunogenicity of INO-3107. Nat Commun  2025, 16,: 1518 https://doi.org/10.1038/s41467-025-56729-6